macitentan + radiotherapy + temozolomide

This is a combination therapy consisting of macitentan, radiotherapy, and temozolomide. Macitentan is an oral dual endothelin receptor antagonist primarily approved for pulmonary arterial hypertension but has been investigated in oncology for its potential to inhibit tumor neovascularization and progression by blocking endothelin A (ET-A) and B (ET-B) receptors, which are upregulated in glioblastoma. Temozolomide is an oral alkylating agent that interferes with DNA replication in cancer cells, leading to cell death; it is standard-of-care chemotherapy for glioblastoma when used with radiotherapy. Radiotherapy uses ionizing radiation to damage the DNA of cancer cells directly. The combination aims to enhance anti-tumor efficacy through complementary mechanisms—macitentan targeting tumor microenvironment signaling pathways, temozolomide providing cytotoxic effects via DNA alkylation, and radiotherapy causing direct DNA damage. This regimen has been studied primarily in the context of newly diagnosed or recurrent glioblastoma.